chr15-74820742-A-C

Variant names:

• chr15-74820742-A-C
• rs1531163
• NM_021819.3:c.882A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021819.3(LMAN1L):​c.882A>C​(p.Lys294Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMAN1L NM_021819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 14 publications found

Genes affected

LMAN1L (HGNC:6632): (lectin, mannose binding 1 like) This gene encodes a mannose-binding type 1 transmembrane protein that contains an N-terminal lectin-like carbohydrate recognition domain. The encoded protein is similar in structure to lectins found in leguminous plants. This lectin is thought to transport newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. [provided by RefSeq, Jan 2017]

ENSG00000261606 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081771016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN1L	NM_021819.3	c.882A>C	p.Lys294Asn	missense_variant	Exon 8 of 14	ENST00000309664.10	NP_068591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1L	ENST00000309664.10	c.882A>C	p.Lys294Asn	missense_variant	Exon 8 of 14	1	NM_021819.3	ENSP00000310431.5
LMAN1L	ENST00000379709.7	c.846A>C	p.Lys282Asn	missense_variant	Exon 7 of 13	1		ENSP00000369031.3
ENSG00000261606	ENST00000488000.6	n.1412A>C		non_coding_transcript_exon_variant	Exon 6 of 14	2
LMAN1L	ENST00000565585.5	n.1276A>C		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.5
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		0.074
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.052
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.45	P;P
Vest4		0.097
MutPred		0.23		Loss of ubiquitination at K294 (P = 3e-04);.;
MVP		0.25
MPC		0.084
ClinPred		0.60	D
GERP RS		-1.3
PromoterAI		-0.0021	Neutral
Varity_R		0.13
gMVP		0.19
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1531163; hg19: chr15-75113083;